Advances in gastric cancer prevention

Posted by Master, Doctor Mai Vien Phuong - Department of Examination & Internal Medicine - Vinmec Central Park International General Hospital

Stomach cancer is a multifactorial cancer that is numbered among its causes, both environmental and genetic. It is mainly diagnosed in South America and Southeast Asia, where it shows the highest probability rates, and it is diagnosed relatively rarely in Western and North American countries.

Although the molecular mechanisms leading to gastric cancer development are only partially known, three main causes have been well characterized: Helicobacter pylori (H. pylori) infection, a diet rich in foods salt and/or smoked and red meat, and epithelial cadherin (E-cadherin) mutants. Unhealthy diet and H. pylori infection may induce genotypic and phenotypic variation of gastric cancer cells, but their effects may be influenced by a diet rich in vegetables and fresh fruit. Many authors have recently focused their attention on the importance of a well-balanced diet, recommending a necessary eating education starting in childhood. Continuous monitoring is needed in carriers of the mutated E-cadherin gene, as they are more likely to develop stomach cancer, also in the inner layers of the stomach.

H. pylori infection and unhealthy diet induce tumor proliferation and genetic variation, respectively, in gastric cells. In fact, higher levels of methylation were found in both some of the CpG-marked islands and in the promoter region of the microRNA gene in patients with H. pylori infection. On the other hand, high N-nitroso compounds are found in the case of diets high in red meat, while polycyclic aromatic hydrocarbons and heterocyclic amines are typical of high consumption of smoked and grilled foods. All of these compounds have high mutagenic potential, so their introduction through nutrition is an important factor leading to gastric cell carcinogenic transformation. The mechanism by which high consumption of salted foods contributes to gastric cancer development has not been fully elucidated to date, not yet a synergic action with H. pylori and N-nitroso compounds and increased reactivity. inflammation of the gastric epithelium was found.

H. pylori is a gram-negative bacteria that lives in the stomach that can cause gastritis in infected patients. It can survive in the acidic environment of the stomach thanks to its ability to synthesize urease, an enzyme that can neutralize the acidic pH in the stomach. Various articles focused their attention on the important role of cytotoxicity-related genes in pathogenic islet (Cag PAI), vacuum atoxin A and IceA (induced by exposure to epithelium A), whose positivity is specific to different strains of H. pylori, in the clinical response of the patient. More specifically, their data suggest that in the origin of gastric cancer, an important role may be played by the Cag PAI, a group of about 30 genes encoded by a region of 40 kilobases.
Infections are usually treated with triple therapy, based on proton pump inhibitors-clarithromycin-amoxicillin or metronidazole therapy, however this strategy has recently yielded disappointing results. One possible explanation is an increase in H. pylori strains showing resistance to clarithromycin, which has challenged different studies focusing on different treatment regimens. These are based on time-deferred drug administration, known as sequential 10-day therapy, when four drugs are used concurrently, or on both.

Recent articles describe new forms of gastric cancer that develop after H. pylori eradication therapy. Yamamoto et al focused their attention on the phenotypic and genotypic differences in gastric cancer arising in therapy-experienced patients and in untreated, but infected patients. coincide. Instead, Matsuo et al studied patients who had undergone eradication therapy, those who did not, and those who were negative for H. pylori infection.
The results obtained by the two groups showed differences in gastric cancer patterns arising in patients treated for H. pylori eradication, Yamamoto found the prevalence of diffuse gastric cancer. radiation, while Matsuo found the prevalence of intestinal epithelial-type gastric cancer. These differences suggest the need to consider a higher number of patients, but these studies highlight the possibility of developing gastric carcinoma also after eradication therapy.

According to the International Agency for Research on Cancer, H. pylori is a potent, group 1 carcinogen, as it can cause genetic changes, such as hypermethylation events, that contribute to cell transformation. Therefore, an assistive strategy in preventing the carcinogenicity of H. pylori could be focused on reducing its infectivity. A significant contribution can come from food. The sulforaphane in broccoli has a protective effect in the case of H. pylori infection, as it can induce phase 2 detoxification enzymes, such as glutathione-S-transferase (GST), and may act as a biocide in the tissues of gastric rodents. These data can also be considered in humans, as it has been shown that eradication of H. pylori increases the restored GST level and considers the reduced GST level to be a marker of gastric cancer, as well. due to H. pylori infection.

The stomach is one of the first organs in contact with food, after the lining of the mouth and esophagus, performing the second step of mechanical and chemical digestion. The link between food and stomach cancer development has largely been studied. Many authors have reported that reliable causes of stomach tumors are high intake of red meat, salted and smoked foods. These dietary habits are a source of highly carcinogenic compounds such as N-nitroso compounds, polycyclic aromatic hydrocarbons, and heterocyclic amines.

In countries with high rates of stomach cancer, classified as Southeast Asia, the Maldives and the American Southwest, typical dishes include fish and vegetables, fresh and salted, fermented and pickled fruits. In 1990, Tsugane et al. published their results highlighting that the Japanese population living in Hawaii showed a lower incidence of stomach cancer, if compared with the Japanese population in Sao Paulo, Brazil. Brazilian dietary habits include foods with a high N-nitrogen potential such as grilled red meat and fish, crustaceans and fried vegetables with a lot of salt.
Other studies focusing on the link between stomach cancer and salt intake analyzed salt excretion in 24-hour urine samples of subjects 75 years of age and younger, and it found an association. nearly linear correlation between cumulative mortality from gastric cancer in five different regions of Japan. Furthermore, Okinawa, the prefecture with the lowest stomach cancer mortality rate in Japan, has a dietary habit that includes the lowest salt intake in the whole of Japan. Thus, the association between gastric tumors and salted foods has been confirmed by various ecological and epidemiological studies, but the details of the biological mechanisms involved are still unclear. .

E-cadherin, also known as Cadherin type 1 (CDH1), is a cell adhesion glycoprotein first characterized in human cell lines by Shimoyama et al. Its role in gastric cancer development was first identified by Guilford et al., who identified a G → T nucleotide substitution in the donor consensus binding sequence of exon 7 in the Maori. This mutation produces a truncated protein that ultimately results in decreased production of E-cadherin.
The examined family shows early onset of gastric cancer characterized by a diffuse pattern, as the other two families describe carriers of a frameshift mutation in exon 15 and an early stop codon at exon 13, respectively. With success, other authors have identified other E-cadherin mutations in different families worldwide.
All of these germline mutations are dominantly inherited, derived from the term Hereditary Gastric Cancer (HDGC), a familial dominant cancer syndrome. Updated criteria established by the International Consortium of Gastric Cancer Linkage specify that the HDGC syndrome must be characterized by histological confirmation of the criteria for gastric dissemination to only one family member, includes people with diffuse gastric cancer before age 40 years with no family history including individuals and families with a diagnosis of both diffuse stomach cancer (including a person before age 50) and breast cancer.

People who belong to families that also have only one of these traits should undergo genetic testing to investigate whether CDH1 is mutated. Although among familial gastroparesis only 1%-3% are CDH1 mutation carriers, positive results should be followed by well-scheduled endoscopy to monitor the first cancerous lesions. .
However, the effectiveness of this strategy may be nullified in cases with small foci, or in the mucosa. In the scientific literature, total gastrectomy is often performed as a prophylactic strategy, and often, it represents a therapeutic strategy, simply because small foci are frequently undetectable by technique. Endoscopic .

Conclusion
Stomach cancer is by far one of the most lethal tumors, especially in South America and Southeast Asia, where the frequency and mortality are highest. Rare cases of HDGC are caused by CDH1 mutations, and their prevention is above all based on ongoing monitoring, often after an actual mutational diagnosis. The number of hereditary non-stomach cancer among predisposing factors for both H. pylori infection and unhealthy diet includes high intake of salted and smoked foods, red meat and alcohol and reduced intake of vegetables and fresh fruit.
Above all, future perspectives regarding gastric cancer prevention are focused on improving strategies against H. pylori and exploring the molecular mechanisms by which a healthy diet can function.
At Vinmec, gastric cancer screening is done through gastric endoscopy with NBI (Narrow Banding Imaging - endoscopy with narrow light band) for clearer mucosal pathological analysis results. compared with conventional endoscopy.
Besides, with the system of Laboratory Department - Vinmec International General Hospital is a synchronous testing center with a full range of fields: Biochemistry, Hematology - Blood Transfusion, Microbiology - Parasitology and Solution Pathology and 3 majors: Biochemistry, Hematology - Blood Transfusion, Microbiology - Parasitology all achieved ISO 15189:2012 certificates. Vinmec Institute of Stem Cell and Gene Technology also screened 15 common cancers in Men and 17 common cancers in Women with only one gene test.
If you have a need for consultation and examination at Vinmec Hospitals under the national health system, please book an appointment on the website for service.

References
Asombang AW, Kelly P. Gastric cancer in Africa: what do we know about incidence and risk factors? Trans R Soc Trop Med Hyg . 2012;106:69-74. [PubMed] [DOI] Dikshit RP, Mathur G, Mhatre S, Yeole BB. Epidemiological review of gastric cancer in India. Indian J Med Paediatr Oncol . 2011;32:3-11. [PubMed] [DOI] Hu J, La Vecchia C, Morrison H, Negri E, Mery L. Salt, processed meat and the risk of cancer. Eur J Cancer Prev . 2011;20:132-139. [PubMed] Dungal N, Sigurjonsson J. Gastric cancer and diet. A pilot study on dietary habits in two districts differing markedly in respect of mortality from gastric cancer. Br J Cancer . 1967;21:270-276. [PubMed] Matsuo T, Ito M, Takata S, Tanaka S, Yoshihara M, Chayama K. Low prevalence of Helicobacter pylori-negative gastric cancer among Japanese. Helicobacter . 2011;16:415-419. [PubMed] Antonio Giordano, Letizia Cito, Advances in gastric cancer prevention, World J Clin Oncol. Sep 10, 2012; 3(9): 128-136